T cell receptor usage in autoimmune disease.

Abstract

Despite dramatic advances in our understanding of the functions and control of the immune system, progress in autoimmune disease remains frustrating. There is no debate as to the clinical significance of the problem. Autoimmune diseases such as rheumatoid arthritis (RA), insulin-dependent diabetes mellitus (IDDM) and multiple sclerosis (MS) represent an ever-increasing burden on global health just as many infectious diseases are brought under control and the prevalence of atherosclerotic disease appears to be falling in many countries. What is frustrating for immunologists is that, although the immune system appears to play a central role in the pathogenesis of such diseases, we know relatively little about the precise antigens that initiate and maintain the immune attack. It is against this background that the interpretation of studies on T cell receptor (TCR) usage in autoimmune disease must be viewed. This line of investigation is now several years old. Indeed, the concept that T cells involved in specific autoimmune disease might utilise a restricted set of TCR genes (known in some circles as the 'V-region hypothesis') arose from definitive observations on TCR usage of T cells implicated in causing the murine disease, experimental allergic encephalomyelitis (EAE). This model continues be a paradigm for the study of T cell homeostasis in autoimmune disease and lessons that arose from it are now being applied to human disease. Unfortunately, the situation in human disease is much less clear [99]. Nevertheless, from the many reports on TCR usage in human autoimmune disease it is possible to distil a picture which offers hope for the future, not only with respect to the ultimate aim of targeted immunotherapy, but also with regard to the information that may be gained as to the pathogenesis of such disorders.